Emergency Department, Hôpital Pitié-Salpêtrière, AP-HP Sorbonne Université.
Groupe de Recherche Clinique (GRC)-14 BIOSFAST, Centre d'Immunologie et des Maladies Infectieuses (CIMI), UMR 1135, Sorbonne Université.
Eur J Emerg Med. 2024 Dec 1;31(6):429-437. doi: 10.1097/MEJ.0000000000001175. Epub 2024 Sep 12.
During a pandemic like COVID-19, hospital resources are constrained and accurate severity triage of the patients is required.
The objective of this study is to estimate the predictive performances of candidate biomarkers for short-term worsening (STW) of COVID-19.
Prospective, multicenter (20 hospitals in Paris) cohort study of consecutive COVID-19 patients with systematic biobanking at admission, during the first waves of COVID-19 in France in 2020 (COVIDeF cohort).
Consecutive COVID-19 patients were screened for inclusion. They were excluded in presence of severity criteria defined by either an ICU admission, mechanical ventilation (including noninvasive ventilation), acute respiratory distress, or in-hospital death before sampling. Routine blood tests measured during usual care and centralized systematic measurement of creatine kinase, C-reactive protein (CRP), procalcitonin, soluble urokinase plasminogen activator receptor (suPAR), high-sensitive troponin T (TnT-hs), N terminal pro-B natriuretic peptide (NT-proBNP), calprotectin, platelet factor 4, mid-regional pro-adrenomedullin (MR-proADM), and proendothelin were performed.
The primary outcome was STW, defined by a severity criteria within 7 days. A backward stepwise logistic regression model and a 'best subset' approach were used to identify independent association, and the area under the receiving operator characteristics (AUROC) was computed.
Five hundred and eleven patients were analyzed, of whom 60 (11.7%) experienced STW. Median time to occurrence of a severity criteria was 3 days. At admission, lower values of eosinophils, lymphocytes, platelets, alanine aminotransferase, and higher values of neutrophils, creatinine, urea, CRP, TnT-hs, suPAR, NT-proBNP, calprotectin, procalcitonin, MR-proADM, and proendothelin were predictive of worsening. Stepwise logistic regression identified three biomarkers significantly associated with worsening: CRP [adjusted odds ratio (aOR): 1.10, 95% confidence interval (95% CI): 1.06-1.15 for a 10-unit increase, AUROC: 0.73 (0.66-0.79)], procalcitonin [aOR: 0.42, 95% CI: 0.22-0.81, AUROC: 0.69 (0.64-0.88)], and MR-proADM [aOR: 2.85, 95% CI: 1.74-4.69, AUROC: 0.75 (0.69-0.81)]. These biomarkers outperformed clinical variables except diabetes and cancer comorbidities.
In this multicenter prospective study that assessed a large panel of biomarkers for COVID-19 patients, CRP, procalcitonin, and MR-proADM were independently associated with the risk of STW.
ClinicalTrials.gov NCT04352348.
在 COVID-19 等大流行期间，医院资源受到限制，需要对患者进行准确的严重程度分诊。
本研究旨在评估候选生物标志物对 COVID-19 短期恶化（STW）的预测性能。
前瞻性、多中心（巴黎 20 家医院）队列研究，对 2020 年法国 COVID-19 第一波期间入院的连续 COVID-19 患者进行系统的生物标志物检测（COVIDeF 队列）。
连续筛选 COVID-19 患者纳入研究。如果存在严重程度标准，包括 ICU 入院、机械通气（包括无创通气）、急性呼吸窘迫或入院前院内死亡，则排除这些患者。在常规护理期间测量常规血液检查，并进行集中系统测量肌酸激酶、C 反应蛋白（CRP）、降钙素原、可溶性尿激酶型纤溶酶原激活物受体（suPAR）、高敏肌钙蛋白 T（TnT-hs）、N 末端 pro-B 型利钠肽（NT-proBNP）、钙卫蛋白、血小板因子 4、中区域前肾上腺髓质素（MR-proADM）和内皮素前体。
主要结局是 7 天内出现严重程度标准的 STW。采用逐步向后逻辑回归模型和“最佳子集”方法来识别独立关联，并计算接收者操作特征曲线下面积（AUROC）。
共分析了 511 例患者，其中 60 例（11.7%）发生了 STW。发生严重程度标准的中位时间为 3 天。入院时，嗜酸性粒细胞、淋巴细胞、血小板、丙氨酸氨基转移酶值较低，中性粒细胞、肌酐、尿素、CRP、TnT-hs、suPAR、NT-proBNP、钙卫蛋白、降钙素原、MR-proADM 和内皮素前体值较高与恶化相关。逐步逻辑回归确定了三个与恶化显著相关的生物标志物：CRP[调整后的优势比（aOR）：1.10，95%置信区间（95%CI）：1.06-1.15，增加 10 个单位，AUROC：0.73（0.66-0.79)]、降钙素原[aOR：0.42，95%CI：0.22-0.81，AUROC：0.69（0.64-0.88)]和 MR-proADM[aOR：2.85，95%CI：1.74-4.69，AUROC：0.75（0.69-0.81)]。这些生物标志物的预测性能优于临床变量，除糖尿病和癌症合并症外。
在这项评估 COVID-19 患者大量生物标志物的多中心前瞻性研究中，CRP、降钙素原和 MR-proADM 与 STW 风险独立相关。
ClinicalTrials.gov NCT04352348。
